title: Clinical trial simulation to assist in COPD trial planning and design with a biomarker-based diagnostic: when to pull the trigger?
abstract: Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous disease with a wide range of clinical phenotypes that vary from predominantly airway disease (chronic bronchitis) to predominantly parenchymal disease (emphysema). Current advances for the treatment of COPD are increasingly focused on targeted treatments and development of novel biomarker-based diagnostics (Dx)'s to select the patients most likely to benefit. Clinical trial planning and design with biomarkers includes additional considerations beyond those for conventional trials in un-selected populations, e.g., the heterogeneity of COPD phenotypes in the population, the ability of a biomarker to predict clinically meaningful phenotypes that are differentially associated with the response to a targeted treatment, and the data needed to make Go/No Go decisions during clinical development. We developed the Clinical Trial Object Oriented Research Application (CTOORA), a computer-aided clinical trial simulator of COPD patient outcomes, to inform COPD trial planning with biomarkers. CTOORA provides serial projections of trial success for a range of hypothetical and plausible scenarios of interest. In the absence of data, CTOORA can identify characteristics of a biomarker-based Dx needed to provide a meaningful advantage when used in a clinical trial. We present a case study in which CTOORA is used to identify the scenarios for which a biomarker may be used successfully in clinical development. CTOORA is a tool for robust clinical trial planning with biomarkers, to guide early-to-late stage development that is positioned for success.
authors.affiliation: 1MedImmune, LLC , Gaithersburg, Maryland , USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Gold
authors.forename: Michelle
authors.initials: M
authors.lastname: Dawson
authors.forename: Harry
authors.initials: H
authors.lastname: Yang
authors.forename: Joseph
authors.initials: J
authors.lastname: Parker
authors.forename: David L
authors.initials: DL
authors.lastname: Gossage
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D002986:Clinical Trials as Topic; D003198:Computer Simulation; D003658:Decision Making, Computer-Assisted; D006801:Humans; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis* / Q000378:metabolism* / Q000628:therapy; D012107:Research Design; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers